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Molecular mechanisms of the asymmetric pit-closing in clathrin-mediated endocytosis

Yu, Yiming 京都大学 DOI:10.14989/doctor.k24983

2023.11.24

概要

1.1 Clathrin-mediated endocytosis in mammals and yeast
Endocytosis is a cellular event necessary for the transportation of extracellular
materials into the cytosol via the deformation of the plasma membrane and the formation of
vesicles. The classic endocytic pathway includes phagocytosis, macropinocytosis,
clathrin/caveolin-mediated endocytosis, and clathrin/caveolin-independent fast and ultrafast
endocytosis (Figure 1-1). Clathrin-mediated endocytosis (CME) is marked by the assembly of
a clathrin coat around the vesicle and is responsible for the regulation of a variety of signal
transduction pathways and cellular events, including epidermal growth factor (EGF)dependent cell proliferation, low-density lipoprotein (LDL) uptake, leading-edge formation
during cell migration, and integrin-mediated focal adhesion disassembly (Figure 1-1) 1–4.
After half a century of study and investigation, a large proportion of the clathrin-dependent
endocytotic machinery has been fully understood, and it is believed that the function and
molecular mechanisms of CME are highly conserved in mammals and yeast. For instance,
CME in mammalian and yeast cells is composed of a series of morphological changes of the
plasma membrane. The membrane is transformed from shallow invaginations to deeplyinvaginated narrow or spherical vesicles connecting to the membrane via a tabulated neck 5–7.
Moreover, aside from clathrin and many of its adaptor proteins, which are strictly required for
the formation of clathrin-coated vesicles (CCV) in mammals and yeast, actin also plays a
critical role in the maturation and transportation of the CCV. In particular, actin filaments
flow to the yeast cytosol to assist the clathrin-driven membrane bending, which resulted from
the high osmotic pressure pushing the membrane toward the cell wall 8, 9; In mammals, actin
assembles around the CCV before its detachment from the membrane and forms a comet tail
attached to the vesicle, which was believed to promote the dynamin-dependent constriction
and scission of tubulated membrane and to boost the transportation of vesicles into the cytosol
. ...

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This thesis is based on material contained in the following scholarly paper(s).

1. Yu, Y. & Yoshimura, S. H. Self-assembly of CIP4 drives actin-mediated asymmetric pitclosing in clathrin-mediated endocytosis. Nat. Commun. 14, 4602 (2023).

2. Yu, Y., & Yoshimura, S. H. Investigating the morphological dynamics of the plasma

membrane by high-speed atomic force microscopy. J. Cell Sci. 134, jcs243584 (2021).

98

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